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      LPAR1, Correlated With Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer

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          Abstract

          Prostate cancer is a common malignancy in men worldwide. Lysophosphatidic acid receptor 1 (LPAR1) is a critical gene and it mediates diverse biologic functions in tumor. However, the correlation between LPAR1 and prognosis in prostate cancer, as well as the potential mechanism, remains unclear. In the present study, LPAR1 expression analysis was based on The Cancer Genome Atlas (TCGA) and the Oncomine database. The correlation of LPAR1 on prognosis was also analyzed based on R studio. The association between LPAR1 and tumor-infiltrating immune cells were evaluated in the Tumor Immune Estimation Resource site, ssGSEA, and MCPcounter packages in R studio. Gene Set Enrichment Analysis and Gene Ontology analysis were used to analyze the function of LPAR1. TCGA datasets and the Oncomine database revealed that LPAR1 was significantly downregulated in prostate cancer. High LPAR1 expression was correlated with favorable overall survival. LPAR1 was involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression was positively correlated with immune infiltrates, including CD4+ T cells, B cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, and natural killer cells. Moreover, LPAR1 expression was positively correlated with those chemokine/chemokine receptors, indicating that LPAR1 may regulate the migration of immune cells. In summary, LPAR1 is a potential prognostic biomarker and plays an important part in immune infiltrates in prostate cancer.

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          Most cited references28

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          Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

          Summary Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.
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            Dendritic Cells and Cancer Immunity.

            Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors. Bypassing suppressive pathways or directly activating DCs can unleash a T-cell response, and although clinical efficacy has proven elusive, therapeutic targeting of DCs continues to hold translational potential in combinatorial approaches.
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              Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer

              Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enzalutamide, which prolongs overall survival among patients with metastatic, castration-resistant prostate cancer, would delay metastasis in men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                10 June 2020
                2020
                : 10
                : 846
                Affiliations
                [1] 1Department of Immunology, The Fourth Military Medical University , Xi'an, China
                [2] 2School of Basic Medicine, The Fourth Military Medical University , Xi'an, China
                Author notes

                Edited by: George Kulik, Wake Forest University, United States

                Reviewed by: Sanja Štifter, University of Rijeka, Croatia; Mohammed Imran Khan, University of Western Ontario, Canada

                *Correspondence: Kun Yang yangkunkun@ 123456fmmu.edu.cn

                This article was submitted to Genitourinary Oncology, a section of the journal Frontiers in Oncology

                †These authors have contributed equally to this work

                Article
                10.3389/fonc.2020.00846
                7325998
                32656075
                227835ea-330c-473d-a427-d2fe3763f455
                Copyright © 2020 Shi, Jiang, Yang, Zhang, Wang, Liu, Sun, Lu and Yang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2019
                : 29 April 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 44, Pages: 10, Words: 5739
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81772763
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                lysophosphatidic acid receptor 1,tumor-infiltrating immune cells,chemokines,migration,prostate cancer

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